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Int J Biol Macromol. 2017 May;98:637-645. doi: 10.1016/j.ijbiomac.2017.02.025. Epub 2017 Feb 10.

Vitamin C down-regulate apo(a) expression via Tet2-dependent DNA demethylation in HepG2 cells.

Author information

1
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001 China.
2
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001 China; The Second Hospital Affiliated to University of South China, Hengyang 421001, Hunan, China.
3
The Second Hospital Affiliated to University of South China, Hengyang 421001, Hunan, China.
4
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001 China. Electronic address: smt121101@163.com.

Abstract

Lipoprotein(a)[Lp(a)] is a risk factor for coronary heart diseases. However, the metabolism of this protein remains poorly understood. Efficient and specific drugs that can decrease high plasma levels of Lp(a) have not been developed yet. Vitamin C is responsible for maintaining the catalytic activity of a group of iron and 2-oxoglutarate (2OG)-dependent dioxygenases and induces the generation of 5-hydroxymethylcytosine (5hmC) via Ten-eleven translocation (Tet) dioxygenases. In addition, It has been reported vitamin C deficiency induces atherosclerosis and increases Lp(a) and apo(a) plasma levels in Lp(a)+ mice. However, the mechanism is still unclear. In this study, we investigated the effects of vitamin C on apo(a) expression and the possible molecular mechanism of vitamin C that influences apolipoprotein(a) [apo(a)] biosynthesis in HepG2 cells. Results showed that vitamin C significantly inhibited the expression and secretion levels of apo(a). Vitamin C can also increase ELK1 expression and hydroxymethylation of ELK1 promoter and the globle DNA in HepG2 cells. In addition, the effects of vitamin C inhibiting the apo(a) expression were attenuated by ELK1siRNA and Tet2siRNA. These results suggested vitamin C down-regulate apo(a) expression via Tet2-dependent DNA demethylation in HepG2 cells.

KEYWORDS:

Apolipoprotein a; Coronary heart diseases; Demethylation; Tet2; Vitamin C

PMID:
28192139
DOI:
10.1016/j.ijbiomac.2017.02.025
[Indexed for MEDLINE]

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